PROJECT SUMMARY Postoperative pulmonary complications (PPCs) are conditions affecting the respiratory tract that adversely influence the clinical course of patients after surgery. PPCs are a major perioperative entity influencing the morbidity and mortality of a large number of patients, and with substantial impact on health care costs. National estimates suggest 1,062,000 PPCs/year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. Although PPCs are as significant and lethal as cardiac complications, research in this area has received much less attention, and well established perioperative strategies to minimize PPCs are regrettably limited. Recently, our and other groups have suggested a crucial role of anesthesia related interventions such as ventilatory strategies, and administration and reversal of neuromuscular blocking agents in reducing PPCs, findings that are consistent with the beneficial effects of lung protective ventilation during the adult respiratory distress syndrome (ARDS). Surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the start of surgery. Yet, intraoperative anesthetic and abdominal surgery interventions result in lung derecruitment and can predispose to or produce direct and indirect lung injury. Thus, effective anesthetic strategies specifically aiming at early lung protection are greatly needed. Yet, there is substantial lack of data on strategies to avert PPCs, leading to the current unsatisfactory anesthetic practice on PPC prevention. Based on our previous findings, we propose an anesthesia-centered bundle to optimize perioperative lung recruitment and reduce PPCs. It consists of optimal mechanical ventilation comprising individualized positive end-expiratory pressure (PEEP) to maximize respiratory system compliance and minimize driving pressures; individualized use of neuromuscular blocking agents and their reversal; and postoperative lung expansion and early mobilization. We propose to conduct a prospective multicenter randomized controlled pragmatic trial with blinded assessor to compare PPCs in 750 patients undergoing major open abdominal surgery receiving an optimal individualized anesthetic- centered management bundle composed of those interventions versus usual care. We hypothesize that this anesthesia-centered bundle, focused on perioperative pulmonary recruitment, will minimize multiple and synergistic factors responsible for the perioperative pulmonary dysfunction and reduce the rate of PPCs. To test this hypothesis, we will compare the participant's PPC severity using a previously published 5-point scale based on the most serious PPC during the first seven days after surgery between intervention groups. As the statistical and data coordinating center for the study we will: ensure rigorous study design; meticulous implementation of the study in collaboration with the clinical coordinating center; and perform comprehensive data analysis. Our plan for widespread dissemination of results will change clinical practice by establishing a new, clinically feasible anesthesia-centered strategy to reduce PPCs after open abdominal surgery.